莫达非尼对大鼠肠缺血再灌注损伤的保护作用研究

Protective effect of modafinil on intestinal ischemia-reperfusion injury in rats

目的评价莫达非尼(Mod)对肠缺血再灌注损伤大鼠的保护作用。方法将45只Wistar大鼠随机分为假手术组、对照组和实验组,每组15只。假手术组仅进行开腹和探索肠系膜上动脉,不做动脉闭塞操作。对照组和实验组正常构建肠缺血再灌注损伤(I/R)模型。术前7 d起,实验组大鼠每天腹腔注射10 mg·kg^(-1) Mod的二甲基亚砜(DMSO)溶液,假手术组、对照组大鼠每天注射等量DMSO。用分光光度法检测肠道组织氧化应激水平;用酶联免疫方法检测肠道组织炎症因子水平。结果假手术组,对照组和实验组大鼠的肠道丙二醛水平分别为(21.21±3.25),(48.92±5.89)和(35.78±6.64)nmol·g^(-1);白细胞介素^(-1)β分别为(48.69±8.16),(76.06±9.85)和(62.56±7.16)pg·g^(-1);肿瘤坏死因子-α分别为(53.72±6.98),(109.51±10.58)和(81.76±9.42)pg·g^(-1);Caspase-3分别为(3.89±1.63),(15.02±5.84)和(9.65±5.11)ng·g^(-1)。以上指标,实验组与对照组比较,差异均有统计学意义(均P<0.05)。结论Mod前治疗可以改善肠损伤,可能是潜在的治疗药物,可以预防I/R引起的肠损伤这一重大临床挑战。

Objective To evaluate the protective effect of modafinil(Mod)on intestinal injury caused by intestinal ischemia-reperfusion injury.Methods Forty-five Wistar rats were randomly divided into 3 groups,namely sham-operated group,control group and experimental group,with 15 rats in each group.The sham-operated group only underwent opening and exploration of the superior mesenteric artery,without arterial occlusion.The control and experimental groups were constructed as normal intestinal ischaemia-reperfusion(I/R)models.In the experimental group,a daily dose of 10 mg·kg^(-1) Mod dimethyl sulfoxide(DMSO)solution was administered intraperitoneally to the animals from seven days prior to surgery.The animals in the sham-operated and control groups were injected intraperitoneally with an equivalent dose of DMSO daily for seven days prior to surgery.The levels of intestinal oxidative stress levels were measured by enzyme-linked immunoassay;the levels of intestinal inflammatory factor levels were measured by enzyme-linked immunoassay.Results The intestinal malondialdehyde levels in the sham-operated,control and experimental rats were(21.21±3.25),(48.92±5.89)and(35.78±6.64)nmol·g^(-1);interleukin^(-1)βwas(48.69±8.16),(76.06±9.85)and(62.56±7.16)pg·g^(-1);tumor necrosis factor-αwas(53.72±6.98),(109.51±10.58)and(81.76±9.42)pg·g^(-1);the caspase-3 was(3.89±1.63),(15.02±5.84)and(9.65±5.11)ng·g^(-1).There were statistically significant differences between control group and experimental group(all P<0.01).Conclusion Pre-Mod treatment can improve intestinal injury and therefore it can be considered as a potential therapeutic agent to prevent the major clinical challenge of I/R-induced intestinal injury.